Strep throat is an infection of the pharynx caused by the bacteria Streptococcus pyogenes. The pharynx is that part of the throat between the tonsils and the larynx, or voice box. The main pathogenic beta-hemolytic strep groups for humans are A, C and G. More than 90% of streptococcal disease in humans may be caused by Group A beta-hemolytic strep (GABHS), although Group C is becoming increasingly recognized as an under-diagnosed condition.
Streptococcus pyogenes is the bacterial cause of several human infections including acute pharyngitis, impetigo, acute rheumatic fever and scarlet fever. The particular bacterium associated with these diseases are beta-hemolytic streptococci (BHS) of Groups A, C and G, of which Group A is the most dominant pathogen.
The bacteria that cause streptococcal infection such as strep throat emit toxins that result in inflammation. The initial locale of the infection is the pharyngeal mucosa. These toxins are central in facilitating the progression of the infection. Symptoms of strep throat include a sore throat that starts suddenly, without runny nose or congestion. The throat is extremely red, and swallowing is painful. White patches typically appear on the tonsils, and lymph nodes in the neck swell. Symptoms may also include fever, headache, loss of appetite and fatigue. Children with strep throat may also exhibit nausea, vomiting and abdominal distress.
Existing tests for determining when severe sore throat symptoms may be a strep infection, such as GABHS, require a visit to a physician's office or clinical laboratory. The most commonly used in-office test is an antigen-based test, specific to GABHS. These rapid strep tests require a deep swab sample of the mucus from the pharyngeal area, which is prepared using one or two reagent chemicals. The test is considered adequate for Strep A (GABHS) positive readings (sensitivity), and takes about 3-15 minutes, but negative readings (specificity) may require additional testing. When a negative rapid strep test occurs, it is common practice to perform a laboratory cell culture to confirm or rule out the presence of a Strep A infection. The culture is required owing to a high incidence of false negatives associated with the antigen specificity of current tests. Exemplary of these tests are those disclosed in U.S. Pat. Nos. 4,863,875; 5,374,538 and 6,030,835.
People who may be at risk for serious complications from strep infection include people who have chronic conditions such as diabetes, weakened immune systems or immunodeficiency disorders. Serious complications from untreated strep infection include otitis media, peritonsillar abscesses, meningitis, peritonitis, scarlet fever and rheumatic fever. Prompt diagnosis and treatment with antibiotics is the best ways to prevent infection spread and complications.
The current rapid tests require swabbing the back of the throat and tonsils to obtain a mucus sample and transferring the sample to a container or test paper. The swabbing of the throat represents a traumatic event for a patient, as well as the healthcare worker. The collection of a throat swab is made all the more difficult with pediatric patients who represent a strep-vulnerable population. With the current antigen-based tests the addition of two or more reagents is required before a visual check for the development of a color indicator. The color development is a result of GABHS antigens reacting with the antibodies introduced by the test. The methodology is sufficiently complicated to require a laboratory technician to properly perform the test, and it is too complicated for use by non-professionals.
Most sore throat symptoms, however, are due to upper respiratory viruses, and do not require immediate or extended medical care. Specifically, Group A beta-hemolytic streptococci is cultured in only approximately 15% to 20% of children with sore throats. In other words, as many as 80% of office visits are unnecessary, and “could” be avoided if a means were available for screening patients with sore throat symptoms before they seek medical care, to determine if the cause of the symptoms is associated with a virus or bacteria.
BHS Groups A, C, and G produce toxins that are known as spreading agents or invasions. One such toxin that has been well documented is streptokinase. Streptokinase is specific to these several forms of streptococcal basteria, which makes is a potential valuable biomarker for the presence of the bacteria. Streptokinase possesses no intrinsic catalytic activity but binds to plasminogen resulting in conformational expression of an active catalytic site on the zymogen without the usual strict requirement for peptide bond cleavage. Plasminogen is the zymogen of the broad-spectrum serine protease plasmin, which degrades fibrin clots and other extracellular matrix (ECM) components such as fibronectin, laminin, vitronectin, and proteoglycans. Plasminogen is activated to its enzyme state (plasmin) by the host activator tissue plasminogen activator. Plasminogen activation is a critical component in establishing invasive bacterial infections. Subversion of the host plasminogen system renders a pathogen capable of degrading ECM proteins and activating a cascade of metalloproteases, thereby conferring the potential to invade host tissue barriers. Plasmin is subsequently produced by proteolytic cleavage and the resulting streptokinase-plasmin complex propagates plasminogen activation through expression of a substrate recognition exosite.
Thus, there exists an opportunity for a non-antigen specific rapid test for the presence of clinically significant beta-hemolytic streptococcus (Groups A, C, and G) in a bodily fluid that is operative independent of a mucosal swab and additional purification or visualization enhancement steps. Additionally, there exists a need for a rapid beta-hemolytic streptococcus test that is amenable to home use as a prescreen for consultation with a health professional.